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Rapid Intrabacterial Hydrolysis for Activating Antibiotics against Gram-negative Bacteria

preprint
submitted on 04.03.2019 and posted on 05.03.2019 by Jiaqing Wang, Deani L. Cooper, Wenjun Zhan, Difei Wu, Hongjian He, Shenghuan Sun, Susan T. Lovett, Bing Xu
Antimicrobial drug resistance demands novel approaches for improving the efficacy of antibiotics, especially against Gram-negative bacteria. Here we report that conjugating a diglycine (GG) to a prodrug of antibiotics drastically accelerates intrabacterial hydrolysis of ester bond for regenerating the antibiotics against E. coli. Specifically, the attachment of GG to chloramphenicol succinate (CLsu) generates a novel conjugate (CLsuGG), which exhibits about an order of magnitude higher inhibitory efficacy than CLsu against E. coli. This work, for the first time, illustrates that dipeptide conjugation modulates intrabacterial hydrolysis for increasing antibiotic efficacy and reducing adverse drug effects.

History

Email Address of Submitting Author

bxu@brandeis.edu

Institution

Brandeis University

Country

USA

ORCID For Submitting Author

0000-0002-4639-387X

Declaration of Conflict of Interest

no conflict of interest

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